Elsevier

Biochemical Pharmacology

Volume 30, Issue 11, 1 June 1981, Pages 1353-1358
Biochemical Pharmacology

Characterization of eight biogenic indoleamines as substrates for type A and type B monoamine oxidase

https://doi.org/10.1016/0006-2952(81)90320-8Get rights and content

Abstract

Tryptamine, N-methyltryptamine, N,N-dimethyltryptamine, 5-hydroxytryptamine (5-HT), 5-hydroxy-N-methyltryptamine, bufotenine, 5-methoxytryptamine, and 5-methoxy-N,N-dimethyltryptamine were characterized as substrates for type A and type B monoamine oxidase (MAO) in rat liver mitochondria. Experiments on sensitivity to clorgyline and to deprenyl, using two substrate concentrations, showed that tryptamine and its N-methylated and N,N-dimethylated derivatives were common substrates for both types of MAO at a substrate concentration of 20.0 μM; at 1000 μM, tryptamine and N-methyltryptamine were common, but N,N-dimethyltryptamine became specific for type B MAO. All the 5-hydroxy- or 5-methoxy-indole derivatives were almost completely specific for type A MAO at a substrate concentration of 20.0 μM; when the concentration was 1000 μM, some of the MAO activity was due to type B MAO for 5-HT, bufotenine and 5-methoxytryptamine. The rat liver mitochondrial enzyme was pretreated with 10−7M clorgyline and 10−7M deprenyl to obtain, respectively, the type B-rich and the type A-rich enzyme. These enzyme preparations were subjected to kinetic analyses for the eight amines. From the kinetic analyses, together with data on inhibitor sensitivity, the following phenomena can be described. N-Methylation of tryptamine or of 5-HT did not cause appreciable changes in the specificity of the substrates toward each type of MAO, but it elevated the Kmvalue of type B MAO when the values for tryptamine and N-methyltryptamine were compared. N,N-Dimethylation of tryptamine and 5-HT tended to increase the specificity for type B MAO. All the dimethylated compounds had very low activities with either type A or type B MAO. Either the 5-hydroxy- or the 5-methoxy-group contributed to the specificity of the substrates for type A MAO.

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